ABSTRACT
In spite of the advances in immunotherapy and targeted therapies, lung cancer continues to be the leading cause of cancer-related death. The epidermal growth factor receptor is an established target for non-small cell lung cancer (NSCLC), and its overactivation by the ligands can induce accelerated proliferation, angiogenesis, and metastasis as well as proinflammatory or immunosuppressive signals. CIMAvax-EGF is an epidermal growth factor (EGF)-depleting immunotherapy that is approved for the treatment of NSCLC patients in Cuba. The study was designed as a phase IV trial to characterize the safety and effectiveness of CIMAvax-EGF in advanced NSCLC patients treated in 119 community polyclinics and 24 hospitals. CIMAvax-EGF treatment consisted of four bi-weekly doses followed by monthly boosters. Overall, 741 NSCLC patients ineligible for further cancer-specific treatment were enrolled. CIMAvax-EGF was safe, and the most common adverse events consisted of mild-to-moderate injection site reactions, fever, chills, tremors, and headache. For patients completing the loading doses, the median survival was 9.9 months. For individuals achieving at least stable disease to the frontline and completing vaccination induction, the median survival was 12 months. Most of the functional activities and symptoms evaluated through the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire improved over time. In conclusion, this real-world trial demonstrated that CIMAvax-EGF was safe and effective in patients who were vaccinated in the maintenance scenario. A larger effect was seen in subjects with poor prognosis like those with squamous tumors and high EGF levels. Remarkably, this community-based intervention was very important because it demonstrated the feasibility of treating advanced lung cancer patients with active immunotherapy in primary care institutions. In addition to CIMAvax-EGF, patients received supportive care at the community clinic. Vaccine administration by the family doctors at the polyclinics reduced the patients' burden on the medical oncology services that continued providing chemotherapy and other complex therapies. We conclude that community polyclinics constitute the optimal scenario for administering those cancer vaccines that are safe and require prolonged maintenance in patients with advanced cancer, despite the continuous deterioration of their general condition. Clinical trial registration: https://rpcec.sld.cu/trials/RPCEC00000205-En, identifier RPCEC00000205.
ABSTRACT
Introducción: Conocer las alteraciones en exámenes de laboratorio clínico, es de utilidad en el diagnóstico y el progreso de pacientes con la COVID-19. Objetivo: Describir los parámetros de laboratorio clínico en pacientes diagnosticados con la COVID-19. Métodos: Estudio descriptivo en 82 pacientes hospitalizados con la COVID-19. Las variables analizadas fueron edad, sexo, comorbilidad, reporte de paciente, estado al egreso, hemoglobina, recuento de glóbulos blancos, conteo absoluto de neutrófilos, conteo absoluto de linfocitos, conteo de plaquetas, eritrosedimentación, dímero D, creatinina, urea, alanina aminotransferasa, aspartato aminotransferasa, #947;-glutamil transpeptidasa, fosfatasa alcalina, lactato deshidrogenasa, relación neutrófilos/ linfocitos y de plaquetas/ linfocitos. Resultados: La edad promedio fue de 55,61 ± 22,04, fue mayoría el sexo femenino (57,3 por ciento), hipertensos (41,5 por ciento), el 18,3 por ciento reportados de grave y el 14,6 por ciento falleció. La edad avanzada y la comorbilidad se asociaron al reporte de gravedad. Hubo disminución significativa de la hemoglobina, linfocitos; elevación de la eritrosedimentación, dímero D, creatinina, #947;-glutamil transpeptidasa y lactato deshidrogenasa, sobre todo en graves. La relación neutrófilos/ linfocitos y de plaquetas/ linfocitos alertaron sobre el agravamiento del paciente y la posibilidad de fallecer. Conclusiones: Los pacientes tenían una media de edad de 55,61, del sexo femenino, con hipertensión arterial; egresaron vivos, reportados de no graves. Disminuyen los valores medios de hemoglobina, conteo global de los linfocitos, sobre todo en graves; aumenta el dímero D, creatinina, ALT, AST, ALP, GGT, y LD. La relación neutrófilos/ linfocitos y de plaquetas/ linfocitos muestran valores medios altos, sobre todo en graves y en quienes fallecieron (AU)
Introduction: Knowing the alterations in clinical laboratory tests is useful in the diagnosis and progress of patients with COVID-19. Objective: To describe the clinical laboratory parameters in patients diagnosed with COVID-19. Methods: Descriptive study in 82 hospitalized patients with COVID-19. The variables analyzed were age, sex, comorbidity, patient report, discharge status, hemoglobin, white blood cell count, absolute neutrophil count, absolute lymphocyte count, platelet count, erythrocyte sedimentation rate, D-dimer, creatinine, urea, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, alkaline phosphatase, lactate dehydrogenase, neutrophil / lymphocyte and platelet / lymphocyte ratio. Results: The average age was 55.61 ± 22.04, the majority were female (57.3 percent), hypertensive (41.5 percent), 18.3 percent reported serious and 14.6 percent died. Advanced age and comorbidity were associated with the severity report. There was a significant decrease in hemoglobin, lymphocytes; elevated erythrocyte sedimentation rate, D-dimer, creatinine, γ-glutamyl transpeptidase, and lactate dehydrogenase, especially in severe patients. The neutrophil / lymphocyte and platelet / lymphocyte ratio warned about the worsening of the patient and the possibility of death. Conclusions: The patients a mean age of 55.61, female, with arterial hypertension; they were discharged alive, reported as not serious. Mean hemoglobin values decrease, global lymphocyte count, especially in severe patients; increases D-dimer, creatinine, ALT, AST, ALP, GGT, and LD. The neutrophil / lymphocyte and platelet / lymphocyte ratio show high mean values, especially in severely ill patients and in those who died(AU)
Subject(s)
Aspartate Aminotransferases , Blood Sedimentation , Creatinine , Alanine Transaminase , COVID-19 , Reference Standards , Comorbidity , Clinical Laboratory TechniquesABSTRACT
Worldwide, there has been a progressive demographic shift over the past 50 years resulting in a larger proportion of older adults in the general population. Aging itself is a complex biological phenomenon characterized in part by changes in the immune system known as "immunosenescence", which makes older adults more susceptible to infectious, cardiovascular and autoimmune diseases, as well as cancers. Several strategies have been proposed in an attempt to reverse immunosenescence, including use of hormones, cytokines and thymic factors. A promising drug in the search to restore the thymic microenvironment (which plays an important role in the regulation and maintenance of the immune system) in older adults is Biomodulina T, a Cuban product registered for use in patients with recurrent respiratory infections. The administration of Biomodulina T increases the number of naïve T-lymphocyte, CD4-positive cells that have recently migrated from the thymus gland (recent thymic emigrants) and memory CD8-positive T lymphocytes, which have characteristics akin to stem cells (stem cell-like memory). Furthermore, the expression of programmed cell death 1 protein in CD4-positive T lymphocytes and CD4-positive T lymphocytes decreases, and the proliferative capacity of CD4-positive T lymphocytes increases, without changes in the frequency of regulatory T lymphocytes. These results suggest that the administration of Biomodulina T could be used to restore immunity in older adults and in other immunocompromised individuals, improve response to other immunotherapies in cancer patients, and increase the effi cacy of vaccinations in older adults. Its use has been approved in Cuba for immune system restoration.KEYWORDS Immunosenescence, aging, immunotherapy, immuno-modulation, antineoplastic protocols, Cuba.
Subject(s)
Aging/immunology , Immunologic Factors/administration & dosage , Immunosenescence/drug effects , Immunotherapy/methods , Aged , Biological Products , Cuba , HumansABSTRACT
En la actualidad existe un aumento del envejecimiento poblacional en Cuba y a nivel mundial, consecuencia del éxito de las políticas de salud pública y del desarrollo socioeconómico. Con el incremento progresivo de la edad se evidencian cambios en el sistema inmunológico que contribuyen a una susceptibilidad incrementada a las enfermedades infecciosas, condiciones patológicas relacionadas con la inflamación, enfermedades autoinmunes, el cáncer y se manifiesta una respuesta reducida ante la vacunación. La manipulación de la inmunosenescencia a través de diferentes terapéuticas se espera que contribuya al rejuvenecimiento del sistema inmune y por consiguiente a la restauración de la inmunidad en individuos inmunocomprometidos, al control del cáncer y al incremento de la eficacia de la vacunación en ancianos(AU)
There is an increase of population aging in Cuba and globally, as a result of the success of public health policies and socio-economic development. With the progressive increase in age, there are changes in the immune system that contribute to an increased susceptibility to infectious diseases, pathological conditions related to inflammation, autoimmune diseases, cancer and a reduced response to vaccination. The manipulation of immunosenescence through different therapies has been studied. It is expected to possibly contribute to the 'rejuvenation' of the immune system and consequently, to the restoration of immunity in immunocompromised individuals, the improvement of the effectiveness of vaccination in the elderly and the control of cancer(AU)
Subject(s)
Humans , Male , Female , Immunosenescence/immunology , Immunity, Innate/immunology , Population Dynamics , Immune SystemABSTRACT
El proceso de envejecimiento provoca cambios en el sistema inmune que afectan su funcionamiento y desarrollo. Estos cambios pueden manifestarse desde la linfopoyesis hasta la respuesta que orquesta el sistema inmune frente a determinada enfermedad o agente infeccioso. Ambas ramas de la inmunidad, innata y adaptativa, se afectan en este proceso, lo que genera un impacto negativo en la respuesta inmune de los ancianos y los predispone a padecer enfermedades infecciosas, cáncer, autoinmunidad y a desarrollar respuestas pobres tras la administración de vacunas(AU)
The aging process produces functional and developmental changes in the immune system. Those changes may appear from lymphopoiesis up to the final response of the immune system facing a certain disease. Both branches of immunity, innate and adaptive, are affected by the aging process; hence these changes can have a negative impact on the immune response of elderly patients and increase their susceptibility to infectious diseases, cancer and decreased vaccine efficacy(AU)
Subject(s)
Humans , Aged , Aged, 80 and over , Aging/immunology , Lymphopoiesis/immunology , Adaptive Immunity/physiology , Immunity, Active/physiology , Immunity, Innate/physiologyABSTRACT
El proceso de envejecimiento provoca cambios en el sistema inmune que afectan su funcionamiento y desarrollo. Estos cambios pueden manifestarse desde la linfopoyesis hasta la respuesta que orquesta el sistema inmune frente a determinada enfermedad o agente infeccioso. Ambas ramas de la inmunidad, innata y adaptativa, se afectan en este proceso, lo que genera un impacto negativo en la respuesta inmune de los ancianos y los predispone a padecer enfermedades infecciosas, cáncer, autoinmunidad y a desarrollar respuestas pobres tras la administración de vacunas...
The aging process produces functional and developmental changes in the immune system. Those changes may appear from lymphopoiesis up to the final response of the immune system facing a certain disease. Both branches of immunity, innate and adaptive, are affected by the aging process; hence these changes can have a negative impact on the immune response of elderly patients and increase their susceptibility to infectious diseases, cancer and decreased vaccine efficacy...
Subject(s)
Humans , Aged , Aged, 80 and over , Aging/immunology , Immunity, Active/physiology , Adaptive Immunity/physiology , Immunity, Innate/physiology , Lymphopoiesis/immunologyABSTRACT
La molécula CD28 es considerada uno de los receptores coestimuladores más importantes en las células T, necesaria para la completa activación celular. En los últimos años se ha acumulado suficiente evidencia sobre su participación en los mecanismos conocidos como señal 2 de activación celular o coestimuladora. De esta forma se convierte en un blanco atractivo para estrategias terapéuticas en enfermedades autoinmunes y trasplante de órganos. Esta revisión se concentra en los principales mecanismos por los cuales esta molécula participa en la completa activación de las células T(AU)
CD28 is a very important correceptor among T cells and provide positive signals that promote and sustain T-cell responses. In the last few years, CD 28 has become an interesting target in grafts and autoimmune diseases. This review will focus on the mechanisms whereby CD28 allowing a complete T cell activation(AU)
Subject(s)
Humans , CD28 Antigens/therapeutic use , Tumor Necrosis Factor Receptor Superfamily, Member 7/therapeutic use , T-LymphocytesABSTRACT
La molécula CD28 es considerada uno de los receptores coestimuladores más importantes en las células T, necesaria para la completa activación celular. En los últimos años se ha acumulado suficiente evidencia sobre su participación en los mecanismos conocidos como señal 2 de activación celular o coestimuladora. De esta forma se convierte en un blanco atractivo para estrategias terapéuticas en enfermedades autoinmunes y trasplante de órganos. Esta revisión se concentra en los principales mecanismos por los cuales esta molécula participa en la completa activación de las células T
CD28 is a very important correceptor among T cells and provide positive signals that promote and sustain T-cell responses. In the last few years, CD 28 has become an interesting target in grafts and autoimmune diseases. This review will focus on the mechanisms whereby CD28 allowing a complete T cell activation
Subject(s)
Humans , /therapeutic use , /therapeutic use , T-LymphocytesABSTRACT
BACKGROUND: The progressive decline in the immune function during ageing is termed immunosenescence. Previous studies have reported differences between males and females in the distribution and cell responses of lymphocyte subsets. Most studies of immunosenescence have been done in populations of industrialized countries living in a rather cold environment, and facing lower antigenic challenges such as Cytomegalovirus (CMV). The aim of this study was to determine the effect of ageing on lymphocytes in a population with a high prevalence of CMV infection in all ages, and to compare gender differences related to the immunosenescence markers. RESULTS: Different populations of peripheral blood leukocytes from healthy young and old IgG-CMV seropositive individuals were examined using flow cytometry. With age, the number and frequency of B cells and T cells significantly decreased, while highly differentiated T cells increased. Such changes were different in males and females. The age-associated decline of less differentiated lymphocyte subsets (CD19, CD4 and CD8 cells) and the increase of highly differentiated T cells were more prominent in females. In males, there were no significant changes in CD19, CD4 and CD8 subsets but there was a significant increase in the proportion of highly differentiated T cells. CONCLUSION: Shifts in lymphocyte subsets distribution were influenced by age and gender in an IgG-CMV seropositive population. These results suggest different patterns of immunosenescence in respect to gender differences. These patterns could have implications in the design of immunotherapy in the elderly.
ABSTRACT
Se describe una novedosa técnica anestésica denominada crioanalgesia, que constituye una alternativa para la cirugía de catarata con facoemulsificación. Esta variante anestésica es eficaz para lograr una analgesia adecuada para la cirugía de catarata. Permite que la cirugía sea en régimen ambulatorio, favorece la masividad e implica bajos costos.
An assessment was made on a new anesthetic technique called cryoanalgesia, an alternative for cataract surgery with phacoemulsification. This anesthetic variant is effective to achieve adequate analgesia for cataract since it allows that surgery be performed in outpatient service, favours massive treatment and implies low costs.
Subject(s)
Humans , Diagnostic Techniques, Surgical , PhacoemulsificationABSTRACT
Se describe una novedosa técnica anestésica denominada crioanalgesia, que constituye una alternativa para la cirugía de catarata con facoemulsificación. Esta variante anestésica es eficaz para lograr una analgesia adecuada para la cirugía de catarata. Permite que la cirugía sea en régimen ambulatorio, favorece la masividad e implica bajos costos(AU)
An assessment was made on a new anesthetic technique called cryoanalgesia, an alternative for cataract surgery with phacoemulsification. This anesthetic variant is effective to achieve adequate analgesia for cataract since it allows that surgery be performed in outpatient service, favours massive treatment and implies low costs(AU)
